First, you need to make a unique safe. To do this, simply put 'GenericSafe01' into the filter box of your object window. This should leave only one item in the list on the right hand side. Double click to open its container window.
In the 'ID' box, change where it says 'GenericSafe1' to something of your own, like 'aaMySafe01'. In the right hand box, you can change what items are in the safe. Either edit whats already there using the 'Objects' dropdown menu underneath, or add a new item by right clicking in the box and selecting 'new'. When you're ready, click OK. When it asks if you want to create a new form, click yes.
Find your new safe in the object window, and drag it across to the cell you're trying to edit. You'll be able to see it in the world view. Double click on it to open the 'Reference' window. Here you'll see a number of tabs. Click on the 'Lock' tab, and then click on the 'locked' tickbox. You will then be able to click the 'level' dropdown menu, and select 'very hard'.
Click OK, and you're down. Now you just need to place it, find it ingame, and you'll need a lockpick skill of 100 to open it.
Hope that helps.