Temozolomide and Radiation Therapy With or Without Cediranib Maleate in Treating Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

* Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization \[WHO\] grade IV) confirmed by central review prior to step 2 registration
* Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of MGMT status

  * Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged
  * Cavitron ultrasonic aspirator (CUSA)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged
  * Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis
  * The tumor tissue must be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue may not be submitted later than 28 days after the surgical procedure, because tissue analysis will not be able to be performed in time for treatment to commence by the mandatory 6-week post-surgery outer limit; submission of tissue earlier than 28 days post-surgery is highly recommended
* The tumor must have a supratentorial component
* History/physical examination, including neurologic examination, within 14 days prior to step 2 registration
* The patient must have recovered from the effects of surgery, post-operative infection, and other complications before step 2 registration
* A diagnostic contrast-enhanced magnetic resonance imaging (MRI) of the brain must be performed preoperatively and postoperatively prior to step 1 registration; the postoperative scan must be performed within 28 days prior to step 1 registration
* Documentation of steroid doses/concurrent medications within 14 days prior to step 2 registration
* Karnofsky performance status \>= 70 within 14 days prior to step 2 registration
* Complete blood count (CBC)/differential obtained within 14 days prior to step 2 registration on study, with adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3
* Platelets \>= 100,000 cells/mm\^3
* Hemoglobin \>=10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) \>= 10.0 g/dl is acceptable)
* Adequate renal function, as defined below:
* Blood urea nitrogen (BUN) =\< 30 mg/dl within 14 days prior to step 2 registration
* Creatinine =\< 1.7 mg/dl within 14 days prior to step 2 registration
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 3 x normal range within 14 days prior to step 2 registration
* Systolic blood pressure =\< 140 mm Hg AND diastolic pressure =\< 90 mm Hg within 14 days prior to step 2 registration in the presence or absence of a stable regimen of anti-hypertensive therapy
* Prothrombin time/international normalized ratio (PT INR) \< 1.4 for patients not on warfarin confirmed by testing within 1 week of step 2 registration
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet both of the following criteria:

  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  * In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
* Patient must provide study specific informed consent prior to step 1 registration
* Women of childbearing potential and male participants must practice adequate contraception
* For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria:

* Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
* Recurrent or multifocal malignant gliomas
* Metastases detected below the tentorium or beyond the cranial vault
* Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide or cediranib); prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
* Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
* Severe, active co-morbidity, defined as follows:

  * Unstable angina and/or congestive heart failure requiring hospitalization
  * Transmural myocardial infarction within the last 6 months
  * Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration
  * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
  * History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
  * Serious and inadequately controlled cardiac arrhythmia
  * Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
  * Evidence of bleeding diathesis or coagulopathy
  * Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
  * Active connective tissue disorders, such as lupus or scleroderma, which in the opinion of the treating physician may put the patient at high risk for radiation toxicity
  * Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Pregnant or lactating women
* Prior allergic reaction to temozolomide
* Patients treated on any other therapeutic clinical protocols within 30 days prior to step 1 registration or during participation in the study
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib
* Mean QTc \>500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome or other significant ECG abnormality noted within 14 days of treatment
* Patients receiving concurrent vascular endothelial growth factor (VEGF) inhibitors are prohibited from participating in this study
* Patients must not be on enzyme-inducing anti-epileptic drugs (EIAED); patients may be on non-enzyme inducing anti-epileptic drugs (NEIAED) or may not be taking any anti-epileptic drugs; in patients who have previously been on EIAED there must be at least a 14 day period since the last dose of an EIAED before the first dose of cediranib