Neurocognitive Outcomes In Patients Treated With Radiotherapy For Five Or More Brain Metastases

Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological confirmation is required (e.g. from extra- or intra-cranial disease).
* If an open biopsy is performed, the patient must be at least one week post biopsy. This requirement does not apply to patients who undergo stereotactic biopsies.
* Patients with ≥5 measurable brain metastases on a diagnostic-quality contrast-enhanced magnetic resonance imaging (MRI) obtained within 30 days prior to registration.
* Patients with ≤10 cc largest tumor volume, and ≤15 cc total tumor volume.
* History/physical examination within 30 days prior to registration.
* Age ≥18 years.
* Karnofsky performance status ≥70 (RTOG recursive partitioning analysis (RPA) Class I \& II).
* Minimum pre-treatment oNCF score ≥70.
* Patients must provide study-specific informed consent prior to study entry.
* Women of child-bearing age must have a negative, quantitative serum pregnancy test ≤14 days prior to study entry, or have a documented reason why such a test is not necessary (e.g. history of tubal ligation).
* Patients must be able to speak and read English fluently (required for the use of online NCF testing).
* Patients must demonstrate basic computer literacy skills and have access to an internet terminal (required for the use of online NCF testing).

Exclusion Criteria:

* Clinical (e.g. multiple new cranial nerve deficits in the absence of obvious radiographic disease to explain symptoms) or radiographic evidence of leptomeningeal disease.
* Patients with measurable brain metastasis(es) resulting from small cell lung cancer and/or germ cell malignancy.
* No documentation of prior cytotoxic or other therapy for malignancy if such therapy was previously received. Note: This does not apply to patients with synchronous metastases at initial diagnosis.
* Contraindication to MR imaging, such as implanted metal devices or foreign bodies, severe claustrophobia, or contraindications to contrast agent administration.
* Estimated glomerular filtration rate (eGFR) \<60 within 6 weeks prior to registration. • Prior radiation therapy to the brain. • Severe, active co-morbidity, defined as follows:

  * Unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months.
  * Transmural myocardial infarction within the last 6 months. - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization, or precluding study therapy at the time of registration.
  * Uncontrolled, clinically significant cardiac arrhythmias. - Radiologic or clinical evidence of hydrocephalus, or history of previously treated hydrocephalus.
* Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study is potentially teratogenic