Optimizing Neurocognition With Whole Brain Radiation Therapy (WBRT) Using Upfront Pulsed Reduced Dose-Rate (PRDR) Technique

Inclusion Criteria:

1. Age ≥18 years at diagnosis of brain metastases.
2. Eastern Cooperative Oncology Group (ECOG) Performance Score of <2.
3. Participants must have a biopsy-proven solid malignancy (histologic proof orunequivocal cytologic proof solid tumor malignancy from either the primary or anymetastatic site) with intracranial lesions radiographically consistent with orpathologically proven to be brain metastases.
4. Patients who have undergone prior systemic therapy are eligible.
5. Life expectancy from extracranial disease greater than six months.
6. Patients with measurable brain metastasis.
7. Patients may have had prior therapy for brain metastasis, including stereotacticradiosurgery (SRS)and surgical resection. Patients must have completed prior therapyby at least 7 days prior to study enrollment for SRS and at least 14 days for surgicalresection
8. If an open biopsy is performed, the patient must be at least one-week post-biopsy.This requirement is not necessary for stereotactic biopsies.
9. Creatinine clearance is ≥ 30 mL/min.
10. Start of PRDR WBRT within two weeks following registration.
11. Ability to complete the Neurocognitive Function (NCF) test battery (including peoplewhose primary language is English).
12. Patients with previous or other malignancies whose disease is controlled and notimpacting ECOG performance or life expectancy.
13. Willing and able to give consent and to comply with treatment and follow-up schedule.

Exclusion Criteria:

1. Metastases from hematological malignancy, or central nervous system malignancy.
2. Patients whose malignancy is being treated with curative intent.
3. Leptomeningeal metastases.
4. Contraindication to MRI imaging with contrast.
5. Contraindication to memantine including concurrent use of N-methyl-D-aspartate (NMDA)antagonists.
6. Stage IV-V chronic kidney disease or end-stage renal disease.
7. Participants with a maximum tumor diameter exceeding 5 cm (if not resected).
8. Prior cranial whole brain radiation therapy.
9. Past medical history of dementia which is thought to be unrelated to the brainmetastases.
10. Women of childbearing potential who are known to be pregnant or are unwilling to usean acceptable method of contraception from the time of informed consent untilcompletion of the course of radiotherapy.
11. Patients must not have a serious medical or psychiatric illness that would, in theopinion of the treating physician, prevent informed consent or completion of protocoltreatment, and/or follow-up visits.
12. Non-native English speakers will be excluded since patients often lose their facultywith the language they acquired second before their native language is affected in thecontext of cognitive decline. This could adversely affect performance on verbalcognitive tasks.