This study will be a dual-arm prospective longitudinal cohort study for patients with brain metastases, at least one of which is appropriate for radiotherapy, to explore brain and cognitive changes following SRS or WBRT and evaluate the feasibility of a novel MRI protocol to identify potential radiological biomarkers of NCF decline.

Patients diagnosed with brain mets will be assigned to either Arm A or Arm B, depending on their treatment plan. Patients in Arm A will be treated with SRS. Patients in Arm B will be treated with WBRT.

Patients' neurocognitive function will be assessed before their radiation treatment and followed up for 2 years post treatment.

Inclusion Criteria:

• Patients with brain metastases will be included in this study. Patients with known malignancies but without brain metastases, or patients with primary brain tumors are not eligible for enrollment.
• MRI confirmed 1-10 lesions. Each lesion must not be intended for resection.
• No prior radiation therapy for brain tumours.
• For patients enrolled to arm B, ability to tolerate RespirAct. Based on studies in patients with severe cerebrovascular disease, an 8 - 16% drop-out rate at the time of the first exposure to RespirAct CVR testing is expected [9]. The fourth generation of this device has been associated with increased tolerability secondary to elimination of a physical rebreathing circuit replaced by a digital re-breath analog. This improvement is expected to achieve a drop-out rate significantly below 10%.
• Patients must have a GPA greater than or equal to 1.0.
• Patients must be able to provide informed consent. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Patients must have sufficient fluency in English and sufficient motor and visual functioning (corrected or assisted as required) to complete the NCF-A battery.
• Patients must be accessible for treatment, AE assessment and follow- up.
• Limit to KPS ≥ 70 for patients in arm B; no limit for arm A
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive. Women of childbearing potential will have a pregnancy test to determine eligibility.

Exclusion Criteria:

• Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.

• Pregnant patients will be excluded from this study.

• Prior cranial radiotherapy

• Inability to complete MRI with contrast of the head, or a known allergy to gadolinium

• Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor.

• Patients with known malignancies but without brain metastases.

• Image Findings

  • Widespread definitive leptomeningeal metastasis
  • A brain metastasis that is located ≤ 2 mm of the optic chiasm
  • Evidence of midline shift
  • Fourth ventricular narrowing, concerning for hydrocephalus

• Patients who have undergone surgical resection of brain tumor are not eligible for enrollment.

Patients with brain metastases, at least one of which is appropriate for radiotherapy