The survival of patients with CNS metastases often remains limited to some months. CNS metastases are also associated with neurological decline and decrease of quality of life. An early identification of CNS metastases may potentially lead to more therapeutic options and prevent or delay the development of neurological symptoms and signs. Patients with cancer associated with a high risk of developing CNS metastasis will be enrolled in this trial. These patients are candidates for a screening brain MRI program in the routine management as recommended in current guidelines (Le Rhun et al. 2021) (Amaral et al. 2025, "ESMO Living Guideline: Cutaneous Melanoma, v1.0 February 2025").

The primary objective is to compare the time to CNS metastases diagnosis detected by MRI using different contrast agents (of gadopiclenol at a dose of 0.1 mmol/kg over current standard practice ) in patients with cancer considered at high risk of developing brain metastases.

Inclusion Criteria:

1. Patients with histologically confirmed HER-2 positive or triple negative breast cancer, non-small cell lung cancer, or melanoma
2. Up to 3 months after diagnosis of a cancer at high risk of CNS metastasis with indication for screening and follow-up by MRI (based on a high risk of CNS metastases according to EANO ESMO brain metastases guidelines: stage IV HER-2 positive or triple negative breast, stage II to IV lung cancer, stage IV melanoma)
3. Enrolment at the time of initiation of screening and follow-up MRI: usually, but not necessarily at the time of new diagnosed stage IV HER-2 positive or triple negative breast, lung cancer, melanoma
4. 18 years or older on day of signing informed consent
5. Karnofsky performance status (KPS) ≥ 60
6. Patients must have preserved renal function (serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 30 mL/min (using the Cockcroft-Gault formula)
7. Women of child-bearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test before the MRI.
8. Patients of childbearing / reproductive potential must agree to use adequate birth control measures, as defined by the investigator, during the study period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
9. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
10. Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Exclusion Criteria:

1. Any contraindication to MRI, including claustrophobia
2. Known severe adverse drug reaction or contraindication to gadolinium-based contrast agents
3. Acute or chronic renal insufficiency: grade III or more (eGFR <60 mL/min/1.73 m2) based on one eGFR assessment performed within one day the MRI prior to the first contrast agent injection.
4. Heart failure: class III/IV NYHA
5. Severe liver disease
6. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
7. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
8. Women who are pregnant or who breast feeding