Terameprocol in Treating Patients With Recurrent High Grade Glioma

Inclusion Criteria:

* Patients must have histologically confirmed supratentorial high grade glioma (grade III or IV glioma) that is progressive or recurrent following radiation therapy and chemotherapy; patients with grade IV glioma must have progressed or recurred after initial treatment with radiation and temozolomide; patients with grade III glioma must have received at least radiation and one regimen of chemotherapy (temozolomide or procarbazine, lomustine, vincristine \[PCV\] regimen)

  * Patients must have measurable contrast-enhancing disease by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to undergo MRI of the brain with gadolinium
  * Patients may have had treatment for an unlimited number of prior relapses
  * Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:

    * 12 weeks from the completion of radiation
    * 6 weeks from a nitrosourea chemotherapy
    * 3 weeks from a non-nitrosourea chemotherapy
    * 4 weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
    * 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
    * 4 weeks from prior antiangiogenesis therapy (approved or investigational) (e.g., bevacizumab, aflibercept, ramucirumab, cediranib, cabozantinib, etc.)
  * Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  * Patients must be 18 years of age or older
  * Absolute neutrophil count \>= 1,500/mcL
  * Platelets \>= 100,000/mcL
  * Hemoglobin \>= 9 g/dL
  * Total bilirubin =\< institutional upper limit of normal
  * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal
  * Creatinine =\< institutional upper limit of normal OR creatinine clearance \>= 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal
  * Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =\< 1.5 x institutional upper limit of normal
  * Patients must be able to provide written informed consent
  * Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug
  * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for \>= five years
  * Patients must be able to swallow oral medications
  * Part 2 (surgical) patients only: patients must be undergoing surgery that is clinically indicated as determined by their care providers; patients must be eligible for surgical resection according to the following criteria:

    * Expectation that the surgeon is able to resect at least 100 mg of tumor from enhancing tumor and at least 100 mg from non-enhancing tumor with low risk of inducing neurological injury

Exclusion Criteria:

* Patients receiving any other investigational agents are ineligible
* Patient must not have known sensitivity to terameprocol or any formulation excipients
* Patients with (mean of triplicate) QTc(F) \>/= 450mS on screening 12-lead triplicate electrocardiogram (ECG) are ineligible
* Patients must not be on any anticoagulation
* Patients on any moderate or strong cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9) inducer (e.g., carbamazepine, rifampin) or inhibitor (e.g., amiodarone, fluconazole) are ineligible; CYP2C9 poor metabolizers will not be excluded
* Patients on narrow-therapeutic drugs that are substrates for cytochrome P450 family 1, subfamily A, polypeptide 2 (CYP1A2), CYP2C9, cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19), and cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, phenytoin, pimozide, quinidine, sirolimus, tacrolimus, theophylline, tizanidine, warfarin)
* Patient must not have prior gastrointestinal (GI) surgery or GI disease that might interfere with the absorption of terameprocol
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with terameprocol
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy